Modifications are produced by therapeutic agents whether they be cancer chemotherapeutic drugs or radiation. These include cell killings and production of perturbation in the cell cycle of surviving (as well as the reproductively dead) cells. As the surviving population recovers from that effect, there is a reassortment of the cells to one of any age distribution containing S and G2-M cells. There is also a "reactivation" of the nonproliferating cells into a proliferating compartment. There is also a temporary distortion of the recovering cell population to one of more cycling and proliferating. The most important consideration for tumor therapy would be to transfer the nonproliferating compartment to the proliferating compartment whereupon the greatest variety of potential cancer antimetabolite drugs can be applied. At the same time, if therapeutic ratio and normal tissue tolerance are to be optimized, one must consider the cell kinetics of normal tissues by sequencing and scheduling therapy to minimize the toxic effects of the drugs. When multiple agents or modalities are combined, the proper sequence of therapies is likely to greatly affect their effectiveness and is relevant to human therapy as we have found for the mouse system. Our research aims to study an experimental tumor system to define effects of therapeutic agents and combined modality therapy by defining cell kinetics and optimal sequencing and scheduling.